This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (110)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Pulmonary Diseases  • Asthma  • Randomized Controlled Trial  • Immunology  • Allergy  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Robert F. Lemanske, Jr, MD; Christine A. Sorkness, PharmD; Elizabeth A. Mauger, PhD; Stephen C. Lazarus, MD; Homer A. Boushey, MD; John V. Fahy, MD; Jeffrey M. Drazen, MD; Vernon M. Chinchilli, PhD; Timothy Craig, DO; James E. Fish, MD; Jean G. Ford, MD; Elliot Israel, MD; Monica Kraft, MD; Richard J. Martin, MD; Sami A. Nachman, MD; Stephen P. Peters, MD, PhD; Joseph D. Spahn, MD; Stanley J. Szefler, MD; for the Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute

JAMA. 2001;285:2594-2603.

Context  Inhaled long-acting ₂-agonists improve asthma control when added to inhaled corticosteroid (ICS) therapy.

Objective  To determine whether ICS therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting ₂-agonist to their treatment regimen.

Design and Setting  A 24-week randomized, controlled, blinded, double-dummy, parallel-group trial conducted at 6 National Institutes of Health–sponsored, university-based ambulatory care centers from February 1997 through January 1999.

Participants  One hundred seventy-five patients aged 12 through 65 years with persistent asthma that was suboptimally controlled during a 6-week run-in period of treatment with inhaled triamcinolone acetonide (400 µg twice per day).

Intervention  Patients continued triamcinolone therapy and were randomly assigned to receive add-on therapy with either placebo (placebo-minus group, n = 21) or salmeterol xinafoate, 42 µg twice per day (n = 154) for 2 weeks. The entire placebo-minus group was assigned and half of the salmeterol group (salmeterol-minus group) was randomly assigned to reduce by 50% (for 8 weeks) then eliminate (for 8 weeks) triamcinolone treatment. The other half of the salmeterol group (salmeterol-plus group) was randomly assigned to continue both salmeterol and triamcinolone for the remaining 16 weeks (active control group).

Main Outcome Measure  Time to asthma treatment failure in patients receiving salmeterol.

Results  Treatment failure occurred in 8.3% (95% confidence interval [CI], 2%-15%) of the salmeterol-minus group 8 weeks after triamcinolone treatment was reduced compared with 2.8% (95% CI, 0%-7%) of the salmeterol-plus group during the same period. Treatment failure occurred in 46.3% (95% CI, 34%-59%) of the salmeterol-minus group 8 weeks after triamcinolone therapy was eliminated compared with 13.7% (95% CI, 5%-22%) of the salmeterol-plus group. The relative risk (95% CI) of treatment failure at the end of the triamcinolone elimination phase in the salmeterol-minus group was 4.3 (2.0-9.2) compared with the salmeterol-plus group (P<.001).

Conclusions  Our results indicate that in patients with persistent asthma suboptimally controlled by triamcinolone therapy alone but whose asthma symptoms improve after addition of salmeterol, a substantial reduction (50%) in triamcinolone dose can occur without a significant loss of asthma control. However, total elimination of triamcinolone therapy results in a significant deterioration in asthma control and, therefore, cannot be recommended.

Author Affiliations: Departments of Pediatrics, University of Wisconsin Medical School (Dr Lemanske) and Medicine, University of Wisconsin School of Pharmacy, Madison (Dr Sorkness); Health Evaluation Sciences (Drs Mauger and Chinchilli) and Medicine (Dr Craig), Milton S. Hershey Medical Center, Hershey, Pa; Medicine, University of California at San Francisco (Drs Lazarus, Boushey, and Fahy); Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (Drs Drazen and Israel); Thomas Jefferson University, Philadelphia, Pa (Dr Fish and Peters); Harlem Hospital Center, New York, NY (Drs Ford and Nachman); Departments of Medicine (Drs Kraft and Martin) and Pediatrics (Drs Spahn and Szefler) National Jewish Medical and Research Center, Denver, Colo.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLES

Long-Acting {beta}2-Agonist Monotherapy vs Continued Therapy With Inhaled Corticosteroids in Patients With Persistent Asthma: A Randomized Controlled Trial
, , , , , , , , , , , , , , , , , , and
JAMA. ;285():2583-2593.
FULL TEXT  

Therapeutic Options for Persistent Asthma

JAMA. ;285():2637-2639.
FULL TEXT  

May 23/30, 2001
JAMA. ;285():2655-2656.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Pharmacotherapy of asthma: regular treatment or on demand?
Montuschi et al.
Ther Adv Respir Dis 2009;3:175-191.
ABSTRACT  

An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations: Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice
Reddel et al.
Am. J. Respir. Crit. Care Med. 2009;180:59-99.
ABSTRACT | FULL TEXT  

Asthma Therapies Revisited: What Have We Learned?
Lemanske
Proc Am Thorac Soc 2009;6:312-315.
ABSTRACT | FULL TEXT  

Asthma
Fanta
NEJM 2009;360:1002-1014.
FULL TEXT  

Patient Factors Used by Pediatricians to Assign Asthma Treatment
Okelo et al.
Pediatrics 2008;122:e195-e201.
ABSTRACT | FULL TEXT  

Meta-analysis: Effects of Adding Salmeterol to Inhaled Corticosteroids on Serious Asthma-Related Events
Bateman et al.
ANN INTERN MED 2008;149:33-42.
ABSTRACT | FULL TEXT  

Global strategy for asthma management and prevention: GINA executive summary
Bateman et al.
Eur Respir J 2008;31:143-178.
ABSTRACT | FULL TEXT  

Irvin et al.
Am. J. Respir. Crit. Care Med. 2007;176:521-522.
FULL TEXT  

Randomized Comparison of Strategies for Reducing Treatment in Mild Persistent Asthma
The American Lung Association Asthma Clinical Rese
NEJM 2007;356:2027-2039.
ABSTRACT | FULL TEXT  

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?
Travers et al.
Thorax 2007;62:219-223.
ABSTRACT | FULL TEXT  

Combination Therapy with a Long-Acting beta-Agonist and a Leukotriene Antagonist in Moderate Asthma
Deykin et al.
Am. J. Respir. Crit. Care Med. 2007;175:228-234.
ABSTRACT | FULL TEXT  

Improvements in Distal Lung Function Correlate With Asthma Symptoms After Treatment With Oral Montelukast
Kraft et al.
Chest 2006;130:1726-1732.
ABSTRACT | FULL TEXT  

Sequence, Haplotype, and Association Analysis of ADRbeta2 in a Multiethnic Asthma Case-Control Study
Hawkins et al.
Am. J. Respir. Crit. Care Med. 2006;174:1101-1109.
ABSTRACT | FULL TEXT  

Safety and effectiveness of long-acting inhaled beta-agonist bronchodilators when taken with inhaled corticosteroids.
Ernst et al.
ANN INTERN MED 2006;145:692-694.
ABSTRACT | FULL TEXT  

A Safety Review of Long-Acting {beta}2-Agonists in Patients With Asthma
Rider and Craig
JAOA: Journal of the American Osteopathic Association 2006;106:562-567.
ABSTRACT | FULL TEXT  

Considerations in the long-term management of asthma in ambulatory patients
Williams
Am J Health Syst Pharm 2006;63:S14-S21.
ABSTRACT | FULL TEXT  

beta-Adrenoceptor Polymorphisms: Focus Moves to Long-Acting beta-Agonists.
Tattersfield and Harrison
Am. J. Respir. Crit. Care Med. 2006;173:473-474.
FULL TEXT  

beta-Adrenergic Receptor Polymorphisms and Response to Salmeterol
Wechsler et al.
Am. J. Respir. Crit. Care Med. 2006;173:519-526.
ABSTRACT | FULL TEXT  

Asthma: One Hundred Years of Treatment and Onward
Chu and Drazen
Am. J. Respir. Crit. Care Med. 2005;171:1202-1208.
ABSTRACT | FULL TEXT  

What Is New with the {beta}2-Agonists: Issues in the Management of Asthma
Kelly
The Annals of Pharmacotherapy 2005;39:931-938.
ABSTRACT | FULL TEXT  

Prostanoid DP Receptor Variants and Asthma
Morita et al.
NEJM 2005;352:837-838.
FULL TEXT  

Asthma Steroid Pharmacogenetics: A Study Strategy to Identify Replicated Treatment Responses
Weiss et al.
Proc Am Thorac Soc 2004;1:364-367.
ABSTRACT | FULL TEXT  

Review: inhaled long acting {beta}2 agonists are effective and safe in stable chronic asthma
Parameswaran
EDUCATION AND PRACTICE 2004;89:ep80-ep80.
FULL TEXT  

Making Sense of Asthma Genes
Cookson and Moffatt
NEJM 2004;351:1794-1796.
FULL TEXT  

Review: inhaled long acting {beta}2 agonists are effective and safe in stable chronic asthma
Parameswaran
Evid. Based Med. 2004;9:139-139.
FULL TEXT  

Biofeedback Treatment for Asthma
Lehrer et al.
Chest 2004;126:352-361.
ABSTRACT | FULL TEXT  

Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids
Tantisira et al.
Hum Mol Genet 2004;13:1353-1359.
ABSTRACT | FULL TEXT  

Pharmacologic Interventions to Reduce the Risk of Asthma Exacerbations
O'Byrne
Proc Am Thorac Soc 2004;1:105-108.
ABSTRACT | FULL TEXT  

Ethical Assessment of Clinical Asthma Trials Including Children Subjects
Coffey et al.
Pediatrics 2004;113:87-94.
ABSTRACT | FULL TEXT  

Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial
Pauwels et al.
Eur Respir J 2003;22:787-794.
ABSTRACT | FULL TEXT  

Airway-stabilizing effect of long-acting {beta}2-agonists as add-on therapy to inhaled corticosteroids
Currie et al.
QJM 2003;96:435-440.
ABSTRACT | FULL TEXT  

Stepping down inhaled corticosteroids in asthma: randomised controlled trial
Hawkins et al.
BMJ 2003;326:1115.
ABSTRACT | FULL TEXT  

OTHER ARTICLES NOTED (Nov 01 to 18 Oct 02)
Evid. Based Nurs. 2003;6:e1-1.
FULL TEXT  

Inhaled Corticosteroid Reduction and Elimination in Patients with Persistent Asthma Receiving Salmeterol (SLIC)
Goldsobel
Pediatrics 2002;110:457-458.
FULL TEXT  

ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB
Evid. Based Med. 2002;7:3-3.
FULL TEXT  

Salmeterol and Inhaled Corticosteroids in Patients With Persistent Asthma
Botkin et al.
JAMA 2001;286:3075-3078.
FULL TEXT  

Inhaled Long-Acting {beta}2-Agonists in Asthma Treatment
JWatch General 2001;2001:1-1.
FULL TEXT  

Long-Acting {beta}2-Agonist Monotherapy vs Continued Therapy With Inhaled Corticosteroids in Patients With Persistent Asthma: A Randomized Controlled Trial
Lazarus et al.
JAMA 2001;285:2583-2593.
ABSTRACT | FULL TEXT  

Therapeutic Options for Persistent Asthma
Holgate
JAMA 2001;285:2637-2639.
FULL TEXT